Presenilin 1 plays a central catalytic role in the gamma-secretase processing of amyloid precursor protein, Notch and many other substrates. However, this core component clearly mediates independently several other physiological roles in the cell/neuron. Besides its involvement in beta-catenin degradation, we discuss here the recent implication of presenilin 1 in the turnover of the intercellular cell adhesion molecule, telencephalin, through a degradation route that bears autophagic characteristics. Activation of the endosomal/lysosomal system in general and autophagic degradation in particular, is finally briefly discussed in the context of neurodegenerative diseases.